A glucocorticoid receptor is a 94 kDa ligand-activated intracellular transcriptional factor that is a member of the nuclear receptor superfamily. This receptor is known to affect the regulation of the metabolism of carbohydrates, proteins, fats and the like, suppression of the immune or inflammatory responses, activation of the central nervous system, regulation of cardiovascular function, and basal and stress-related homeostasis and the like due to its transcriptional regulatory action (SOUGOU RINSYOU, 54(7), 1951-2076 (2005), JP-A-2002-193955).
Such drugs which bind to a glucocorticoid receptor have an action of glucocorticoid receptor agonist or glucocorticoid receptor antagonist. However these actions are entirely different and it is determined which action the drugs show by the slight difference of the chemical structures of them.
As typical glucocorticoid receptor agonists, glucocorticoid receptor agonists synthesized in the living body such as cortisol and corticosterone, synthetic glucocorticoid receptor agonists such as dexamethasone, prednisone and prednisolone are known (JP-A-2002-193955). These glucocorticoid receptor agonists are generally called steroids due to having a steroid structure and are applied to the treatment of various diseases.
However, there are some cases that these steroids produce the side effects such as steroid peptic ulcer, steroid purpura, steroid pancreatitis, steroid diabetes, steroid cataract, steroid-induced glaucoma by the use of them (IGAKU DAIJITEN, NANZANDO, The 17th edition, 1038-1040). Therefore to prevent these side effects, it is hoped to create the drug which does not have a steroid structure.
On the other hand, compounds having a 1,2-dihydroquinoline structure are disclosed as glucocorticoid receptor modulators in WO 2004/018429, JP-T-10-0510840, WO 2006/019716 and the like. The range of the compounds disclosed in WO 2004/018429, JP-T-10-0510840, WO 2006/019716 is very wide and they have various chemical structures, and as one of those, the compounds having a 1,2-dihydroquinoline structure are disclosed. However, among those, there is no concrete disclosure that the compound having what kinds of chemical structures have the glucocorticoid receptor agonist action, that is, whether 2,2,4-trimethyl-6-phenyl-1,2-dihydroquinoline derivatives having substituted oxy group have the glucocorticoid receptor agonist action.